The Heidelberg University spinout Revier Therapeutics has left stealth mode after completing a $7 million seed financing round led by the German early-stage life sciences venture fund Khan Technology Transfer Fund II.
Three-year-old Revier will use the money to fund preclinical studies and further develop its pipeline of small-molecule histone deacetylase (HDAC) inhibitors for treatment of cardiac diseases such as heart failure with preserved ejection fraction. In this type of heart failure, the heart pumps normally but does not fill with sufficient blood because it has become stiff and cannot relax properly.
Revier’s technology is based on the work of scientific cofounder Johannes Back, director of the Institute of Experimental Cardiology at Heidelberg University. He and his colleagues focus on class IIa HDACs, which are highly expressed in the heart. They recently discovered that HDAC4 activity can contribute to heart stiffness and that inhibiting this activity improves heart function in animal models.
HDAC enzymes regulate gene expression in cells in response to stressors such as inflammation. The first HDAC inhibitor, vorinostat, was approved in 2006 for treatment of T-cell lymphoma. Several other inhibitors for cancer have also been approved.
But the first-generation HDAC inhibitors are a far cry from the ones Revier is developing, according to the company.
“The first-generation inhibitors were pan-HDAC inhibitors, blocking all classes of HDACs,” says Eva van Rooij, a serial entrepreneur and CEO and cofounder of Revier. “They did show some benefit but additionally a lot of unwanted side effects. Revier’s inhibitors . . . only block pathological enzymatic activity while keeping their canonical function intact.”
A couple of years ago, van Rooij and colleagues started talking about founding Revier. They applied for and won a Golden Ticket from the drug company Novo Nordisk that gave them space in BioLabs Heidelberg, as well as access to scientific expertise and other assistance to build their company.
Another German incubator, the Lead Discovery Center (LDC), was set up by the Max Planck Society and the Khan Technology Transfer Fund to help commercialize academic drug development research. Backs had a prior relationship with the LDC through which he met Mike Nolan, now Revier’s chief technology officer.
“This really accelerated things, because through our collaboration with LDC and Mike, we got our hands on compounds that we can actually use to modulate this pathway for our disease indication,” says van Rooij, who is also a professor at the University Medical Center Utrecht.
Revier is currently selecting a lead compound for heart failure with preserved ejection fraction. It also plans to develop a second candidate to target atherosclerotic cardiovascular disease.
“We’re expecting to nominate a compound as our development candidate within the next few months,” says van Rooij, a cofounder of miRagen Therapeutics and Phlox Therapeutics. “We think we have one. We just need to check some boxes.”
Revier is not the only company exploring second-generation HDAC inhibitors for cardiac indications. California-based Tenaya Therapeutics is developing a class IIb HDAC6 inhibitor to treat heart failure with preserved ejection fraction. Its molecule is already in early Phase 1 trials, but van Rooij contends that Revier’s approach is more likely to succeed than Tenaya’s.
“It’s functioning through the acetylation of tubulins, a very different mechanism from the mechanism we are going after,” she says of Tenaya’s molecule. “We think we are more powerful because we’re actually targeting a whole set of metabolic enzymes.”
People with this type of heart failure have other treatment options, such as SGLT2 inhibitors and glucagon-like peptide 1 receptor agonists, originally designed to treat type 2 diabetes and obesity. “But there’s still a lot of room for improvement,” van Rooij says. “They still need a lot of help, and I think there’s a lot of space still to make it better for these people.”
